Structurally Mapping Antibody Repertoires.

Structurally Mapping Antibody Repertoires.
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DOI:
10.3389/fimmu.2018.01698
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发表时间:
2018
影响因子:
7.3
通讯作者:
Deane CM
Deane CM
中科院分区:
医学2区
文献类型:
--
作者:
Krawczyk K;Kelm S;Kovaltsuk A;Galson JD;Kelly D;Trück J;Regep C;Leem J;Wong WK;Nowak J;Snowden J;Wright M;Starkie L;Scott-Tucker A;Shi J;Deane CM

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每个人都有数百万种不同的抗体。现在可以通过下一代免疫球蛋白基因测序(Ig-seq)来分析这种多样性。该技术产生大容量的b细胞受体序列快照,指示抗体库。在本文中,我们用结构信息丰富了这些大规模序列数据集。用结构数据丰富序列可以更好地近似许多重要特征,例如其结合位点和特异性。在这里,我们描述了抗体管道的结构注释,将大型Ig-seq实验的输出映射到已知的抗体结构。我们在5个独立的Ig-seq数据集上证明了我们的方案的可行性,这些数据集涵盖了来自大约600个个体的大约35万个独特的氨基酸序列。尽管理论上抗体的多样性很大,但我们发现来自此类研究的大多数序列可以可靠地映射到现有结构。
Every human possesses millions of distinct antibodies. It is now possible to analyze this diversity via next-generation sequencing of immunoglobulin genes (Ig-seq). This technique produces large volume sequence snapshots of B-cell receptors that are indicative of the antibody repertoire. In this paper, we enrich these large-scale sequence datasets with structural information. Enriching a sequence with its structural data allows better approximation of many vital features, such as its binding site and specificity. Here, we describe the structural annotation of antibodies pipeline that maps the outputs of large Ig-seq experiments to known antibody structures. We demonstrate the viability of our protocol on five separate Ig-seq datasets covering ca. 35 m unique amino acid sequences from ca. 600 individuals. Despite the great theoretical diversity of antibodies, we find that the majority of sequences coming from such studies can be reliably mapped to an existing structure.
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